We have successfully produced an experimental model of bowel necrosis by injecting platelet-activating factor (PAF) into the abdominal aorta of the rat. The histopathology of the lesions is identical with necrotizing enterocolitis (NEC) or ischemic bowel necrosis in humans. The necrosis is constant, and devoid of any inflammatory component. In addition, there was no significant thrombus formation in the mesenteric vascular bed that might account for the necrosis. All other organs were grossly normal. Microscopically, only the lungs showed increased number of polymorphonuclear leukocytes (PMNs) in the alveolar septae; other visceral organs were unremarkable. The experimental bowel necrosis could be transient with lower doses of PAF, and regressed within 3-4 hours. However, when bacterial endotoxin (LPS) was administered together with PAF, the necrosis was prolonged for hours. Preliminary data suggest that the development of NEC is independent of platelets. However, there was a precipitous drop of WBC count following PAF injection, suggesting the possible involvement of PMNs and other inflammatory cells. In this proposal, we plan to thoroughly investigate the morphological and pathophysiological changes induced by PAF in this model, including study of blood pressure, mesenteric vascular permeability and blood flow, platelet count, WBC count, and changes in hematocrit. We will investigate the roles of various inflammatory cells (including platelets) in the development of bowel necrosis, and study the possibility that one or more secondary mediators such as prostaglandins, thromboxane, leukotrienes, serotonin, and histamine might be involved in the pathogenesis of the lesions; all are closely associated with PAF synthesis or action in other systems. Lastly, we plan to either aggravate or prevent the development of experimental bowel necrosis by various drugs. We believe that to study the pathogenesis of experimental bowel necrosis with our model is likely to contribute to the elucidation of mechanisms of production and prevention of ischemic bowel necrosis and NEC in humans, which remain obscure until today.